Non-Infectious Transfusion Reactions (minus TRALI) Transfusion Medicine Eiad Kahwash,MD,FASCP Transfusion Reactions • ANY unfavorable consequence is considered a transfusion reaction of blood TX • The risks of transfusion must be weighed against the benefits Transfusion Reactions 1. Acute (<24 hours) Transfusion Reactions - Immunologic – 2. Acute Transfusion Reactions - Nonimmunologic – 3. Hemolytic (Physical or Chemical destruction of RBC); Circulatory overload; Air embolus; Hypocalcemia; Hypothermia Delayed (>24 Hours) Transfusion Reaction - Immunologic – 4. Hemolytic ; Graft vs. Host Disease; Posttransfusion Purpura Delayed Transfusion Reactions - Nonimmunologic – 5. Hemolytic; Febrile-non hemolytic; Allergic; Anaphylactic; Transfusion Reaction of Acute Lung injury(TRALI) Iron Overload Infectious Complications of Blood Transfusion Acute (<24 hours) Transfusion Reactions 1. Immunologic – Hemolytic; Febrile-non hemolytic; Allergic; Anaphylactic; Transfusion Reaction of Acute Lung injury(TRALI) 2. Nonimmunologic – Volume overload; Hemolytic (Physical or Chemical destruction of RBC); Air embolus; Hypocalcaemia; Hypothermia Acute Transfusion Reactions Immunologic Acute Hemolytic Transfusion Reaction • Associated with Intravascular Hemolysis • Etiology: Antibodies that activate complements in the vasculature: ABO antibodies are predominant / not the only ones. • Prevention: Give ABO compatible blood. Acute Transfusion Reactions Immunologic • May also occur due to ABO incompatible plasma in platelet products • Very rare; less than 20 case reports, all involving group O platelets • Usually occurs in group A patients or those with anti-A titers greater than 1:1000 • Can prevent by removing plasma from platelets, or limiting number of incompatible group O platelets in a 24 hour period (Archives 2007;131:909) Intravascular Hemolysis Characteristics • Within minutes • IgM &/or IgG antibody • Complement activation • Release of histamine and serotonin Signs may include: • • • Pain along infusion site Shock Abnormal bleeding/DIC/ Hemoglobinemia/uria • Release of cytokines: • Renal failure/ Oliguria, fever, hypotension may progress to…anuria Acute Transfusion Reactions Immunologic Febrile non-hemolytic TX Reactions • An INCREASE in temperature of 1OC during infusion of blood component – Usually “mild & benign” = not life threatening – Can have more severe symptoms, not usually • Non-hemolytic • Incidence of 0.1% of RBC transfusions, 0.1-1.0% of platelet transfusions • Cause: Recipient antibodies to donor WBCs & Cytokines in the transfused blood component. Febrile Transfusion Reactions Seen in… • Multiply transfused patients • Multiple pregnancies • Previously transplanted Must rule out… • Hemolytic transfusion reaction • Bacterial contamination of unit Prevention • Leukocyte reduction (pre-storage reduction may be more effective than post-storage reduction) or plasma removal is also helpful. Acute Transfusion Reactions Immunologic Allergic (Urticarial-Hives) Transfusion Reactions • Etiology: Form of cutaneous hypersensitivity triggered by recipient antibodies directed against: – Donor plasma proteins or – Other allergens (food, medicines) in donor plasma • Begins within minutes of infusion • Characterized by rash and/or hives and itching . • Common (1 per 2000 transfusions) • Usually involves release of histamine. Allergic (Urticarial) Reactions • MUST be sure that the only reaction is the development of urticaria • Must rule out more severe symptoms that could lead to anaphylaxis: – angioneurotic edema – laryngeal edema – bronchial asthma • Prevention: Can pre-treat recipient with anti-histamines before transfusion. (Transfus Med Rev 2007;21:1, Br J Haematol 2005;130:781) . Acute Transfusion Reactions Immunologic Anaphylaxis • Life threatening!! • Etiology: – Recipient is IgA deficient & has anti-IgA in serum – Recipient anti-IgA can react to even small amounts of donor IgA in the plasma in any blood component – Idiopathic &Haptoglobin deficiency • Reaction may occur within minutes : Onset of symptoms is SUDDEN • Prevention: Wash cellular components or blood products from IgA deficients Acta Anaesthesiol Scand 2002;46:1276 Anaphylaxis Symptoms • Burning sensation at infusion site • Coughing, difficulty in breathing, and bronchospasms can lead to cyanosis • Nausea, vomiting, severe abdominal cramps, diarrhea • Hypotension which can lead to shock, loss of consciousness, & death • MUST STOP TX IMMEDIATELY Acute Transfusion Reactions Immunologic TX Reaction of Acute Lung Iinjury Etiology: • Acute onset of hypoxemia and pulmonary edema on CX-RAY within 6 hrs of TX without evidence of cardiac failure. Mechanism’s • Primary Suspect: Donor antibodies to recipient WBCs • Another cause: Biologically active lipids in the lungs causing edema Transfusion Reaction of Acute Lung Injury(TRALI) • Symptoms • Chills, fever, cough, cyanosis, hypotension, increased difficulty breathing • Prevention: For recipients : give male products- For donors: watch/defer. Acute Transfusion Reactions NONimmunologic Circulatory Overload • Etiology: Rapid increases in blood volume to patient .Risk factors: compromised cardiovascular function, current volume overload, small intravascular volume (elderly, young children), severe chronic anemia. Signs and Symptoms • Dyspnea, cyanosis, severe headaches, hypertension or CHF (congestive heart failure). Chest Xray: pulmonary edema, distended pulmonary artery, cardiomegaly • Laboratory: elevated B-natriuretic peptide (BNP) is 81% sensitive and 89% specific (Transfusion 2005;45:1056) • Prevention: Slow Tx. Treatment: Stop infusion and place patient in sitting position. Archives 2007;131:708 Acute Transfusion Reactions NONimmunologic Physically or Chemically Induced Red Cell Destruction Etiology: • Destruction of red blood cells in the collection bag and infusion of free hemoglobin, etc. Improper temperatures: High or Low • Microwave blood bag, malfunctioning blood warmer or water bath, inadvertent freezing of blood. Physically or Chemically Induced Red Cell Destruction Osmotic Hemolysis • Addition of drugs or hypotonic solutions (5% dextrose, deionized water, etc.) to transfusion. • • • • Mechanical Hemolysis Caused by rollers in blood pump Pressure infusion pumps Small bore needles Prevention: Adherence to procedures for all aspects of procuring, processing, issuing and administering red blood cell transfusions. Acute Transfusion Reactions NONimmunologic Hypocalcemia • Excess citrate: When infused at rate >100 mL/minute or individuals with impaired liver function: – Citrate is broken down by liver. • Seen more in pediatric and elderly patients • Signs and Symptoms: Facial tingling, nausea, vomiting. • Prevention: Slowing or discontinuing infusion. Acute Transfusion Reactions NONimmunologic Hypothermia • Etiology: Drop in core body temperature due to rapid infusion of large volumes of cold blood. • Symptoms: Decreased body temperature and ventricular arrhythmias. • Seen in small infants or massive transfusion • Prevention: Reduce rate of infusion or use blood warmers. Acute Transfusion Reactions NONimmunologic Air Embolism • Etiology: If blood in an open system is infused under pressure or if air enters the system while container or blood administration sets are being changed. • Treatment: Place patient on left side with head down to displace air bubble from pulmonic valve. 1. Acute (<24 hours) Transfusion Reactions - Immunologic – Hemolytic; Febrile-non hemolytic; Allergic; Anaphylactic; Transfusion Reaction of Acute Lung injury(TRALI) 2. Acute Transfusion Reactions - Nonimmunologic – Volume overload; Hemolytic (Physical or Chemical destruction of RBC); Air embolus; Hypocalcemia; Hypothermia 3. Delayed (>24 Hours) Transfusion Reaction - Immunologic – Hemolytic ; Graft vs. Host Disease; Posttransfusion Purpura 4. Delayed Transfusion Reactions - Nonimmunologic – Iron Overload 5. Infectious Complications of Blood Transfusion Delayed (>24 Hours) Transfusion Reaction 1. Immunologic – Hemolytic ; Graft vs. Host Disease; Posttransfusion Purpura 2. Nonimmunologic – Iron Overload Delayed Transfusion Reactions Immunologic Delayed Hemolytic Transfusion Reaction (Red blood cell alloimmunization) • Onset within days (>24 hours) • Associated with Extravascular Hemolysis • Etiology: Antibodies that usually do NOT activate Complements : Rh, Kell, etc. • Prevention: Give antigen negative blood. Extravascular Hemolysis • • • • Characteristics Signs may include: Reaction within days • No release of free Hgb, or enzymes into Antibody attaches to circulation RBC: RBC destroyed in spleen or liver, etc. • May be immediate (hours) or delayed Commonly IgG (days) May or may not activate Complement • Bilirubinemia or bilirubinuria Extravascular Hemolysis Signs & Symptoms continued… 1. Fever or fever & chills 2. Jaundice 3. Unexpected anemia • Some may present as an ABSENCE of an anticipated increase in Hemoglobin and hematocrit. Delayed Transfusion Reaction Immunolgic Graft vs Host Disease (GVHD) • Etiology: Donor CD8+ T-Lymphocytes attack recipient (host) tissues. Very rare in blood stored 4+ days due to WBC inactivation (Br J Haematol 2000;111:146) • Groups at risk: – Immunocompromised patients (Cancer, fetus, neonatal, bone marrow transplant). • Signs: Fever, dermatitis, or erythroderma, hepatitis, diarrhea, pancytopenia, etc. • Prevention: Irradiation of blood products. Osaka City Med J 1999;45:37 Delayed Transfusion Reaction Immunolgic Post-transfusion Purpura • Etiology: Antibodies to platelet antigens (HP1a ) causes abrupt onset of severe thrombocytopenia (platelet count <10,000/l) 5-10 days following transfusion. Usually affects multiparous women . • Signs: Purpura, bleeding, fall in platelet count . treatment: IVIG, plasmapheresis or corticosteroids; platelet transfusions usually NOT recommended Transfus Med 2006;16:69 Delayed Transfusion Reaction NONimmunolgic Iron Overload • • • Etiology: Excess iron resulting from chronically transfused patients such as hemoglobinopathies, chronic renal failure, etc. Signs: Muscle weakness, fatigue, weight loss, mild jaundice, anemia, etc. Treatment: Infusion of deferoxamine - an iron chelating agent has been useful. 1. Acute (<24 hours) Transfusion Reactions - Immunologic – Hemolytic; Febrile-non hemolytic; Allergic; Anaphylactic; Transfusion Reaction of Acute Lung injury(TRALI) 2. Acute Transfusion Reactions - Nonimmunologic – Volume overload; Hemolytic (Physical or Chemical destruction of RBC); Air embolus; Hypocalcemia; Hypothermia 3. Delayed (>24 Hours) Transfusion Reaction - Immunologic – Hemolytic ; Graft vs. Host Disease; Posttransfusion Purpura 4. Delayed Transfusion Reactions - Nonimmunologic – Iron Overload 5. Infectious Complications of Blood Transfusion Infectious Complications of Blood Transfusion (Viral is rare) Infectious Complication of Blood Transfusion Bacterial Contamination • Etiology: At time of collection: either from the donor or the venipuncture site. – During component preparation, etc. • Usually involves endotoxins – Staph, Pseudomonas, E.coli, Yersinia Bacterial Contamination • Components: Most often from platelet components (room temp). Red cell units will look dark. • Symptoms: Rapid onset – Fever, hypotension, shaking chills, muscle pain – Vomiting, abdominal cramps, bloody diarrhea, hemoglobinuria, shock, renal failure, & DIC. Bacterial Contamination Transfusion must be stopped immediately • Gram stain & blood cultures should be done on the unit, patient and all infusion sets . • Broad-spectrum antibiotics should be given immediately intravenously • Prevention: Maintain standards of donor selection, blood collection and proper maintenance of collected blood components. Transfusion Reactions 1. Acute (<24 hours) Transfusion Reactions - Immunologic – Hemolytic; Febrile-non hemolytic; Allergic; Anaphylactic; Transfusion Reaction of Acute Lung injury(TRALI) 2. Acute Transfusion Reactions - Nonimmunologic – Volume overload; Hemolytic (Physical or Chemical destruction of RBC); Air embolus; Hypocalcemia; Hypothermia 3. Delayed (>24 Hours) Transfusion Reaction - Immunologic – Hemolytic ; Graft vs. Host Disease; Posttransfusion Purpura 4. Delayed Transfusion Reactions - Nonimmunologic – Iron Overload 5. Infectious Complications of Blood Transfusion Transfusion Reaction Follow-up Clinical Information Needed: • • • • • Recipient diagnosis Medical history of pregnancy &/or transfusion Current medications Signs & symptoms during transfusion reaction How many mL’s of RBC’s or plasma were transfused? Clinical Information Needed • • • • Were rbc’s cold or warm when transfused? Were red cells infused under pressure? What was the size of the needle used? Were other solutions given through the IV line at the same time? If so what? • Were any other drugs given at the time of transfusion? If so, what? • What were pre- & post- transfusion vital signs? Transfusion Reaction Follow-up Post Transfusion Reaction blood samples to be collected from the recipient: • Clotted specimen • EDTA specimen • Clotted specimen • 1st voided urine specimen post-tx’n • Repeat ABO, Rh, IAT and Crossmatch. Visual check for hemolysis and compare with pre transfusion sample. • DAT (Direct Antiglobulin Test) • Collect 5-7 hours post transfusion to check for bilirubin • Free hemoglobin determination Transfusion Reaction Workup CLERICAL CHECKS 1. Correct identification of patient, specimen, and transfused unit. 2. Agreement of records and history with current results 3. Correct labeling of transfused unit SPECIMEN CHECKS • Visual inspection of post-transfusion specimen • Visual inspection of blood bag and lines Post Transfusion Lab Testing Direct Antiglobulin Test (DAT) • Recipient post-tx’n spec. • Positive: Perform eluate and identify antibody if the pre-TX spec negative. ABO Grouping and Rh Typing • Recipient pretransfusion and posttransfusion specimen • Donor bag. Post Transfusion Lab Testing Indirect Antiglobulin Test (IAT) • Recipient Pre- & post-transfusion reaction specimens • Pre neg and post pos: Identify antibody and compare results of serum panel with eluate panel. In Summery: 1-Allergic: Minor VS Serious 2-Febrile: Minor VS Serious 3-Onset<15 Mints,Temp>1C with other symptoms orTemp>39C, BP , Shock,SOA, Rigors, Back/Chest Pain,Bleeding from IV site, Tachy/Arrhythmia, Nausea/Vomiting and Generalized Flushing In Summery: 1- Stop TX immediately and keep an IV open with 0.9 Saline 2-Contact the clinician 3-Check vital signs every 15 minutes 4-Check labels,forms,and Ids 5-Send bags &patient’s blood to BB 6-Minor(allergic-febrile non-hemolytic) VS Serious (hemolytic &febrile) Questions? Thank You